Intravascular imaging detector

ABSTRACT

An apparatus for intravascular imaging to detect and characterize early stage, unstable coronary arty plaques. The detector works by identifying and localizing plaque-binding beta-emitting radiopharmaceuticals.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application is a divisional of U.S. patent application Ser.No. 09/754,103, filed Jan. 3, 2001, which claims benefit under 37 C.F.R.§1.78 of U.S. Provisional Application No. 60/174,440, filed Jan. 4,2000, and entitled “Intravascular Imaging Detector,” the entire contentsof both of which are incorporated by reference herein. The presentapplication also incorporates U.S. Pat. No. 6,782,289, issued on Aug.24, 2004, by reference herein.

BACKGROUND OF THE INVENTION

Coronary angiography is used to identify and measure the luminaldimensions of blood vessels. Angiography however, cannot provideinformation about plaque content.

The subject invention addresses this deficiency by placing an imagingdetector into the arteries to detect and characterize early-stage,unstable coronary artery plaques. This can provide a signature relevantto the 70% of heart attacks that are caused by minimally obstructive,unstable plaques that are too small to be detected by angiography.

The present invention describes construction of an intravascular imagingdetector which works in concert with systemically administeredplaque-binding beta-emitting radiopharmaceuticals such as18-Fluorodeoxyglucose (18-FDG). The apparatus of the present inventionaccomplishes these benefits by identifying and localizing theseplaque-binding beta or conversion electron emittingradiopharmaceuticals.

Intravascular imaging probes constructed in accordance with theprinciples of the present invention yield detectors, which satisfy thedifficult constraints of the application in terms of size of the device,needed sensitivity, and conformance to the intravascular requirements.

The apparatus of the present invention will allow new targeted and costeffective therapies to prevent acute coronary artery diseases such as:unstable angina, acute myocardial infarction, and sudden cardiac death.

The present invention generally provides an apparatus for intravascularimaging to detect and characterize early-stage, vulnerable coronaryartery plaques. The detector works by identifying and localizingplaque-binding beta-emitting radiopharmaceuticals.

The apparatus of the present invention includes a radiation detector(s)with a predetermined intrinsic spatial resolution, typically between 1-8mm, and preferably between 1-3 mm. In some embodiments, the detector isin the form of a detector array. The detector array can include aplurality of detector units or pixels built onto a single chip orseparate chips. The detector(s) are typically integrated into anintravascular catheter so that it can be manipulated through the bodylumen, optionally using a guidewire in much the same way as a ballooncatheter for angioplasty.

Optionally, the detectors of the present invention can be embeddedwithin a balloon or other expansible structure such as a flexiblemembrane, which is collapsed or deflated during guidance through thebody lumen. The structure can then be deployed at a target site so thatthe detector is pressed up against the inside of the artery wallbringing the detector in contact with the plaque. This optimizes theparticle to gamma and signal to background ratios for charged particleimaging.

During transit through the artery, software or other analyzing means maydecode the data obtained by the detector to operate in a search mode.The search mode is typically performed by summing all of the pixels ofthe detectors to obtain a fast gross count. Once a threshold gross countis detected (e.g. a high count rate region is localized), the softwarecan switch to an imaging mode to produce a higher resolution image toprovide more detail of the plaque. For embodiments using a balloon, theballoon can be kept in a deflated configuration during the fast grosscount and the balloon can be inflated when the detectors are switched tothe imaging mode.

Exemplary radiation detectors include: 1) Scintillators; 2) Imagingplates; 3) Semiconductors; and 4) Ionization chambers. Each of thedescribed embodiments yields a detector which satisfies the difficultconstraints of the application in terms of size of the device, neededsensitivity, and conformance to the intravascular requirements.

The apparatus of the present invention preferably provides both highbeta particle detection efficiency and sufficient sensitivity in thevery small detector volume afforded by an intravascular or other medicalcatheter tip.

Monte Carlo simulations developed for tracking beta trajectories anddeposited energy have been used to guide the choice of material andshape and size of the pixel elements. Whereas the volume of the detectoris limited by the arterial lumen, the correct pixel dimensions(laterally) are comparable with the beta range (in the specificdetector). Monte Carlo simulations have been performed for F-18positrons and T1-204. The simulations have been used as a basis for thedetector design.

The sensitivity has also been directly measured for beta particles foreach of the fabricated prototype detectors. This has been done withT1-204 and F-18 beta emitters.

The apparatus of the present invention allows for high efficiency forbetas and very low detection efficiency for 511 keV gammas. Generally wehave precluded materials that have either high atomic number or highdensity. Gasses, liquids, light plastics and thin low-Z semiconductorshave been found to be preferable in this respect to high Z compoundsemiconductors.

The sensitivity and immunity to gamma background is confirmed with theuse of filter paper disks containing known F-18 source activity. Aseries of measurements is taken from which mean and standard deviationcounts per second is calculated. A second series of the measurements istaken in the same configuration with exception that a 0.2 mm thick pieceof stainless steel is placed in front of detector face this time. Bydividing the results from the first set of measurements by the amount ofthe activity on the disk, the combined (beta and photon) sensitivity iscalculated. The beta sensitivity is calculated by subtracting the purephoton rate from the combined count rate. The results are analyzedversus energy thresholds ranging from the noise level up to 495 keV(Compton edge for 511 keV).

The apparatus of the present invention allows the device to be operatedin such a way as to allow the detector to be pressed up against theinside of the artery wall. Three of the described embodiments: the gasscintillator, the semiconductor detector and the ionization chamberdetector are designed to be embedded within a balloon or otherexpansible structure which although deflated during guidance through theartery or other body lumen, can be inflated when at a plaque site. Theballoon can be alternatively deflated during transit through the arteryand then inflated when at a suspicious suite. In addition the detectorhas the ability to operate in a search mode by summing all of the pixelresponses to obtain a fast gross count during transit through theartery. The apparatus is switched to an “imaging” mode to obtainhigh-resolution detail of the plaque when a high-count rate region islocalized.

The apparatus of the present invention allows for spatial resolution onthe order of 1 mm, which is sufficient to interrogate a plaque. Thisalso is of the same order as the beta range. The spatial resolution isconfirmed by measurement of the point spread function and theinter-element cross talk of the imager to beta particles.

The apparatus of the present invention allows construction to maximizeits passive properties, which are attractive due to the higher degree ofsafety during procedures. The preference had been given to detectorscomposed of inert materials due to the higher degree of safety duringprocedures.

The detection mechanisms of the apparatus of the present invention allowfor the highest signal and sensitivity of the detector. This criterionfavors the semiconductor detector approach, which offers the mostefficient energy transfer.

The apparatus of the present invention allows for a construction thatcan be integrated with the catheter and guidewire.

SUMMARY OF THE INVENTION

The present invention generally provides an apparatus for intravascularimaging to detect and characterize early-stage, vulnerable coronaryartery plaques. The detector works by identifying and localizingplaque-binding beta-emitting radiopharmaceuticals.

The apparatus of the present invention includes a radiation detector(s)with a predetermined intrinsic spatial resolution, typically between 1-8mm, and preferably between 1-3 mm. In some embodiments, the detector isin the form of a detector array. The detector array can include aplurality of detector units or pixels built onto a single chip orseparate chips. The detector(s) are typically integrated into anintravascular catheter so that it can be manipulated through the bodylumen, optionally using a guidewire in much the same way as a ballooncatheter for angioplasty.

Optionally, the detectors of the present invention can be embeddedwithin a balloon or other expansible structure such as a flexiblemembrane, which is collapsed or deflated during guidance through thebody lumen. The structure can then be deployed at a target site so thatthe detector is pressed up against the inside of the artery wallbringing the detector in contact with the plaque. This optimizes theparticle to gamma and signal to background ratios for charged particleimaging.

During transit through the artery, software or other analyzing means maydecode the data obtained by the detector to operate in a search mode.The search mode is typically performed by summing all of the pixels ofthe detectors to obtain a fast gross count. Once a threshold gross countis detected (e.g. a high count rate region is localized), the softwarecan switch to an imaging mode to produce a higher resolution image toprovide more detail of the plaque. For embodiments using a balloon, theballoon can be kept in a deflated configuration during the fast grosscount and the balloon can be inflated when the detectors are switched tothe imaging mode.

Exemplary radiation detectors include: 1) Scintillators; 2) Imagingplates; 3) Semiconductors; and 4) Ionization chambers. Each of thedescribed embodiments yields a detector which satisfies the difficultconstraints of the application in terms of size of the device, neededsensitivity, and conformance to the intravascular requirements.

The apparatus of the present invention preferably provides both highbeta particle detection efficiency and sufficient sensitivity in thevery small detector volume afforded by an intravascular or other medicalcatheter tip.

Monte Carlo simulations developed for tracking beta trajectories anddeposited energy have been used to guide the choice of material andshape and size of the pixel elements. Whereas the volume of the detectoris limited by the arterial lumen, the correct pixel dimensions(laterally) are comparable with the beta range (in the specificdetector). Monte Carlo simulations have been performed for F-18positrons and T1-204. The simulations have been used as a basis for thedetector design.

The sensitivity has also been directly measured for beta particles foreach of the fabricated prototype detectors. This has been done withT1-204 and F-18 beta emitters.

The apparatus of the present invention allows for high efficiency forbetas and very low detection efficiency for 511 keV gammas. Generally wehave precluded materials that have either high atomic number or highdensity. Gasses, liquids, light plastics and thin low-Z semiconductorshave been found to be preferable in this respect to high Z compoundsemiconductors.

The sensitivity and immunity to gamma background is confirmed with theuse of filter paper disks containing known F-18 source activity. Aseries of measurements is taken from which mean and standard deviationcounts per second is calculated. A second series of the measurements istaken in the same configuration with exception that a 0.2 mm thick pieceof stainless steel is placed in front of detector face this time. Bydividing the results from the first set of measurements by the amount ofthe activity on the disk, the combined (beta and photon) sensitivity iscalculated. The beta sensitivity is calculated by subtracting the purephoton rate from the combined count rate. The results are analyzedversus energy thresholds ranging from the noise level up to 495 keV(Compton edge for 511 keV).

The apparatus of the present invention allows the device to be operatedin such a way as to allow the detector to be pressed up against theinside of the artery wall. Three of the described embodiments: the gasscintillator, the semiconductor detector and the ionization chamberdetector are designed to be embedded within a balloon or otherexpansible structure which although deflated during guidance through theartery or other body lumen, can be inflated when at a plaque site. Theballoon can be alternatively deflated during transit through the arteryand then inflated when at a suspicious suite. In addition the detectorhas the ability to operate in a search mode by summing all of the pixelresponses to obtain a fast gross count during transit through theartery. The apparatus is switched to an “imaging” mode to obtainhigh-resolution detail of the plaque when a high-count rate region islocalized.

The apparatus of the present invention allows for spatial resolution onthe order of 1 mm, which is sufficient to interrogate a plaque. Thisalso is of the same order as the beta range. The spatial resolution isconfirmed by measurement of the point spread function and theinter-element cross talk of the imager to beta particles.

The apparatus of the present invention allows construction to maximizeits passive properties, which are attractive due to the higher degree ofsafety during procedures. The preference had been given to detectorscomposed of inert materials due to the higher degree of safety duringprocedures.

The detection mechanisms of the apparatus of the present invention allowfor the highest signal and sensitivity of the detector. This criterionfavors the semiconductor detector approach, which offers the mostefficient energy transfer.

The apparatus of the present invention allows for a construction thatcan be integrated with the catheter and guidewire.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other features of the present invention may be more fullyunderstood form the following detailed description, taken together withthe accompanying drawings, wherein similar reference characters refer tosimilar elements throughout and in which:

FIG. 1 is a schematic view of an apparatus constructed in accordancewith the present invention for intravascular imaging to detect andcharacterize early-stage, unstable coronary artery plaques.

FIG. 2 is a partial cross sectional schematic view of a single-fiberscintillation “camera” employing a scintillating fiber coupled to anoptical fiber.

FIG. 3 is a graph showing the calculated stopping power of electrons upto 2 MeV and the range of electrons in polystyrene up to 1250 keV. A 1mm fiber will stop 300 keV electrons and above 300 the stopping power isclose to 200 keV per mm.

FIG. 4 is a partial cross sectional schematic view of a multi-fiberscintillation “camera” employing a bundle of scintillator fibers eachcoupled to an optical fiber. Physical offset between the fibers will beused to provide position information.

FIG. 5 is fragmentary, exploded perspective view illustrating, insimplified form one embodiment of an apparatus constructed in accordancewith the present invention employing a scintillating fiber “camera”employing a number of different scintillators, each with an emissionspectrum that is offset in wavelength from the others. The detector isreadout by a wavelength dispersing spectrometer.

FIG. 6 is a fragmentary, exploded perspective view illustrating, insimplified form one embodiment of an apparatus constructed in accordancewith the present invention, employing a liquid primary/fiber secondaryscintillation pair detector. In this figure the balloon is deflatedduring guidance through the artery towards a plaque.

FIG. 7 is a fragmented, exploded perspective view illustrating, insimplified form one embodiment of an apparatus constructed in accordancewith the present invention, employing a liquid primary/fiber secondaryscintillation pair detector. In this figure the balloon is inflated inthe artery at the site of plaque.

FIG. 8 is a fragmentary, exploded perspective view illustrating theoperating principal of the liquid primary scintillator/fiber secondaryscintillator pair.

FIG. 9 is a fragmented, exploded perspective view illustrating theoperating principles of the imaging storage phosphor detector.

FIG. 10 is a fragmentary, exploded perspective view illustrating theoperating principal of the imaging storage phosphor detector wherein aspecially shaped mirror at the front of the optical fiber is used toenhance the excitation and reading process from the imaging storagephosphor detector.

FIG. 11 is a fragmentary, exploded perspective view illustrating, insimplified form one embodiment of an apparatus constructed in accordancewith the present invention, employing strips of semiconductor particledetectors. In this figure the balloon is deflated during guidancethrough the artery towards a plaque.

FIG. 12 is a fragmentary, exploded perspective view illustrating, insimplified form one embodiment of an apparatus constructed in accordancewith the present invention, employing strips of semiconductor particledetectors. In this figure the balloon is inflated in the artery at thesite of plaque.

FIG. 13 is a fragmentary, exploded perspective view illustrating theoperating principal of the inflated balloon with four strips of silicondetectors arranged in the inflated balloon.

FIG. 14A is a fragmentary, exploded perspective view illustrating theoperating principal of the resistive chain connecting the detectorswhich will be used to provide signals, the ratio of the signal to acommon signal can give the position information.

FIG. 14B is a fragmentary, exploded perspective view illustrating theoperating principal of the capacitor chain connecting the detectorswhich will be used to provide signals, the ratio of the signal to acommon signal can give the position information.

FIG. 15 is a fragmentary, exploded perspective view illustrating theoperating principal of the ionization chamber detector showing how thedevice appears when the balloon is collapsed during advancing up thecatheter.

FIG. 16 is a fragmentary, exploded perspective view illustrating theoperating principal of the ion chamber detector, showing how, uponreaching the region of interest the balloon is inflated with Xenon gas.

FIG. 17 is a fragmentary, exploded perspective view illustrating theoperating principal of the ionization chamber with the cathode formed byembedding a set of parallel wires in the balloon.

FIG. 18 is a graph showing the calculated ion pairs produced as afunction of electron energy at various values of the pressure for a 1 mmdetector.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

Referring to FIG. 1 an apparatus for imaging in arteries 12 to detectand characterize early-stage, unstable coronary artery plaques 14 iscomprised of an imaging probe tip 20 which includes a miniature betasensitive detector. It works by identifying and localizingplaque-binding radiopharmaceuticals that emit beta particles 16. Theradiation detector has an intrinsic spatial resolution of approximately1-3 mm. It is integrated into an arterial catheter 70 so that it can bemanipulated through the artery by a guidewire 28 in much the same way asa balloon catheter for angioplasty. The detector of the presentinvention once integrated into the catheter 70 connects to dataacquisition electronics 72 and a computer and display 74, which providesan image of the distribution of plaque.

A specific embodiment of the intravascular imaging probe tip 20constructed in accordance with the principles of the present inventionis comprised of a scintillating fiber 22 coupled to a clear opticalfiber 24 as shown in FIG. 2. Scintillating fibers 22 are detectorsformed by mixing scintillating phosphors (1-2%) with the polystyrenethat forms the core of the most popular plastic optical fiber. By havingthe phosphor in the core, the maximum amount of scintillation light 26will find its way down the clear optical fiber 24 to the photodetector28. The scintillation fiber 22 is coupled to a clear optical fiber 24for the delivery of the light to some distance from the site of theradiation. The simplest form of such a detector for intra-vascularimaging would be a single segment of the scintillating fiber 22 coupledto a single clear fiber 24, which is in turn coupled to a photodetector28. The device would be inserted through a catheter system 70 and bymeasuring the count rate as the device is stepped along the artery, thedistribution of radioactivity would be “imaged”. The key parameters ofthe device are the stopping power of the scintillating fiber for theelectron, the light yields, and the change in light yield if the fiberis bent in the process of being placed in the artery or guided throughit.

Scintillating fibers attached to optical fibers and a photomultipliertube produce strong signals at the photomultiplier in the laboratory.For example, 3-HF scintillating fibers emitting at 535 nanometersirradiated with a 204T1 source, which emits betas at a energy similar to18F produced strong signals at the PMT. Even if the fiber optic istwisted in a series of decreasing diameter loops the strength of thesignal is virtually unchanged down to a 1.5 cm radius of curvature. At1.0 cm the fiber optic becomes permanently distorted. In order toaccommodate tight radii of curvature, bundles of smaller fibers can beused.

The calculated stopping power for electrons up to 2 MeV and the range ofelectrons in polystyrene up to 1.25 MeV are shown in FIG. 3. From thefigure we see that a 1 mm fiber will stop 300 keV electrons and above300 the stopping power is close to 200 keV per mm.

The amount of light produced varies as a function of maximum electronenergy for different beta sources. Light produced by 300 key is adequatefor intravascular imaging. A 1 mm or greater diameter fiber is adequatefor all likely radioisotopes. The device can be constructed using shortsegments of scintillating fibers glued to optical fibers. The light canbe transmitted down lengths of fiber up to several meters. The lightemission is in the range from 400 to 600 nanometers.

Various types of scintillating fibers can be used for the purpose. Sincethe stopping power is essentially the same for all the fibers, the lightyield can be optimized by choice of scintillator, fiber optic, or thelike.

In one embodiment of an intravascular imaging probe tip 20 constructedin accordance with the principles of the present invention a bundle ofscintillating fibers 22 are coupled to clear optical fibers 24 as shownin FIG. 4 wherein the scintillating fibers 22 are offset. The offsetprovides the position information.

One such embodiment starts with seven 0.3 mm scintillating fibers 22 sothat the overall diameter is still ˜1 mm. The stopping power of each ofthe 0.3 mm fibers 22 is high enough to absorb 60 keV, which is adequatefor the intravascular imaging system.

The resolution and sensitivity of the multifiber system is controlled bythe length of the scintillator segments 22. For instance, 2 mm segmentsgive a very high resolution low sensitivity system that covers only 14mm, while 7 mm segments give a low resolution high sensitivity systemthat covers approximately 49 mm. The physical design of this system hassome practical implications in that the leading end is narrow and canget into tighter places than the single fiber system. It should beappreciated however, that in other configurations, the arrays ofscintillators can be distributed along a length between less thanapproximately 5 mm to 50 mm, or more.

In one exemplary arrangement, the probe uses scintillation fiberscoupled with plastic fibers to a position sensitive photomultiplier tube(PSPMT). The scintillation fibers and clear fibers are 5 mm to 7 mm and1.5 m in length, respectively, and 0.5 mm in diameter. There are sixscintillation fibers, each offset by 6 mm to yield an imaging devicewhich surrounds a guide wire. The detector assembly is 1.9 mm indiameter and 38 mm in length. The fibers are surrounded by a thin,flexible, plastic tube to shield it from outside light. The fibers areconnected to the PSPMT with a snap on connector. The PSPMT image isdecoded with software to give a linear image. The imaging probe can alsorun in a mode that has an audio output corresponding to the total levelof detected unstable plaque. The device has been tested by stepping a²⁰⁴T1 point source past detector to verify function. ²⁰⁴T1 betas areclose in energy to ¹⁸F betas. System resolution is 6 mm when the sourceis 1 mm from the detector.

In one embodiment of an intravascular imaging probe tip 20 constructedin accordance with the principles of the present invention a number adifferent scintillator fibers 22 are used, each with an emissionspectrum that is offset in wavelength from the others as shown in FIG.5. A suitable detector can be constructed from commercially availablescintillating fibers that cover the range from less than 400 nanometersto greater than 600 nanometers. The series of segments 22 are stacked asindicated in FIG. 5 with the longest wavelength segment (λ₁) at the tipwith incrementally shorter wavelengths (λ₂-λ_(n)) as one advancedtowards the clear optical fiber 24. The longer wavelength emissions willnot have the energy to excite the fluorescent levels in the shorterwavelength scintillators and should be easily transmitted through thedownstream segments. The light will be transmitted to spectrometer 29that uses a grating or other wavelength dispersive medium to spread outthe light over a position sensitive photodetector. This creates aspectrum from the light emitted from the scintillating fibers and withcalibration there is a one to one correlation between position andwavelength, which is then turned into a linear image of the artery. Asuitable 29 is the CHEM2000-UV-VUS Spectrophotometer by Ocean Optics,Inc.

The types of detectors 20 described in the previous three embodiments ofthe subject invention give a high degree of patient safety in that theyrequire no electrical connections and use no potentially dangeroussubstances and no high pressures.

In one embodiment of an intravascular imaging probe tip 20 constructedin accordance with the principles of the present invention a balloon 30is advanced up the artery 12 in a collapsed state as shown in FIG. 6. A5 cm to 10 cm long scintillating fiber 22 attached to a clear fiber 24,is constructed inside the balloon 30 as shown in FIG. 6 and FIG. 7. Whenthe balloon 30 has reached the region of interest containing a suspectplaque 14, it is inflated with a liquid scintillation solution 32 asshown in FIG. 7. The primary liquid scintillator 32 can provide moremass for stopping power.

The primary liquid scintillator 32 contains the primary fluor, whichabsorbs a beta particle 16 and emits short wavelength primaryscintillation light 34. The core of the scintillating fiber optic 22contains a secondary fluor which efficiently absorbs the photons fromthe primary fluor 34 and them emits longer wavelength light 26 whichtravels down the clear optical fiber 24 as shown in FIG. 8. A slidinglight shield 38 provides position sensitivity as shown in FIG. 7. Duringgross count mode, the sliding light shield 38 can be moved away from thefiber optic 22 to allow radiation to interact with the entire fiberoptic. When in the imaging mode, the sliding light shield 38 can bemoved over the fiber optic 22 to provide position sensitivity. The crosssection of the inflated balloon gives a factor of 2 to 3 bettergeometric efficiently for the betas and the extra thickness stops agreater fraction of the higher energy betas compared with thescintillation fiber embodiments described in FIGS. 2-5. The balloon 30is constructed of a material that is both strong and that will notdissolve in solvents such as toluene, which is typically used in themanufacture of liquid scintillators.

In one embodiment of an intravascular imaging probe tip 20 constructedin accordance with the principles of the present invention ascintillating phosphor imaging plate 40 is formed in the shape of a tube˜5 cm long surrounding a clear optical fiber 24 as shown in FIG. 9. Theimaging plate 40 is used to read the distribution of betas recorded onthe imaging plate. The detector is optimized for stopping beta particles16, and has mechanical flexibility for movement in the arteries 12. Theintravascular imaging probe tip 20 constructed in accordance with theprinciples of the present invention has the capability of integratingthe signal from many beta events in the storage phosphor 40. The storedenergy remains stable until scanned with a laser beam 42 through a clearoptical fiber 24. The same optical fiber 24 is used for delivery of thelaser light 42 and transmission of the read out light 46 correspondingto the stored image as shown in FIGS. 9 and 10. This can be accomplishedwith use of a filter 44 use to the difference between the wavelength ofthe laser excitation light 42 (630 nm) and the wavelength of light 46(400 nm) released upon laser excitation. As can be seen in FIGS. 9 and10 a concave conical shaped mirror 48 can be used at the front of theclear optical fiber 24 to focus the light to an annulus 49, enhancingthe excitation and reading process at the specific desired location. Thescanning of the image can be implemented by movement of the opticalfiber 24 together with its integrated mirror 48 along the image plate40.

In one embodiment of an intravascular imaging probe 20 constructed inaccordance with the principles of the present invention a silicon (orother semiconductor) based beta detector is used for intravascularimaging. The basic detector concept that we will begin with is a stringof individual Si-pin detectors 52 configured in strips 53 as shown inFIG. 11.

As shown in FIG. 12 the individual detector elements 52 will beconnected in series to form flexible linear arrays 50 that can be placedbetween inner 54 and outer 55 layers of a balloon 30 as shown in FIG.11. The balloon 30 will be compressed during guidance through the artery12 to the plaque as shown in FIG. 11. The cardiologist will monitor thesummed signal of all detectors 52 during this transit. When the signalsuggests high uptake and possible unstable plaque the balloon can beinflated so that the detectors are pressed against the plaque 14 in theartery wall 12 as shown in FIG. 12. In one embodiment of this detectorthere are between one and four strips 53 fitted into catheters 70 ofvarious French. A scale drawings of one embodiment of an inflatedballoon 30 with four strips 53 is shown FIG. 13. In the clinical settingthe cardiologist will choose the catheter lumen based on the specificinformation about the state of the patients arteries.

The semiconductor detector based intravascular probe tip 20 can use achain of resistors 56 (or chain of capacitors 56′) connecting thedetectors as shown FIGS. 14A and 14B. The detectors and their readoutchain (a thick film technology) can be placed on a thin flexible PCboard. The signal is read out from either end of the chain (Ladder 1 57and 2 58). The ratio between a common signal and the signal from thechain provides information about which pixel the beta interaction tookplace in.

The detectors 52 of the present invention can operate in thephotovoltaic mode which allows the detector to operate passively, usingthe built-in junction potential.

The detectors 52 of the present invention can operate under a biasvoltage 59 as shown in FIG. 14. The detectors are fabricated usingextremely high resistivity starting material in order to minimize thevoltage that needs to be applied to the detector to deplete it. Si-pindetectors fabricated from >10 kohmcm material yield full depletion withjust 8 volts of applied bias and <800 pA/cm² leakage current. The Sistarting material is polished to 200 microns or thinner. In this casethe dark current can be <5 pA (even at body temperature) for the diodeswith 0.5×0.5 mm² active area.

The detectors 52 of the present invention are fabricated with guard ringstructures to reduce the current. This occupies some space at the edgeof each device. The 5 0.5×0.5 mm² active area devices can be implementedon 0.75×0.75 mm² die.

In one embodiment an intravascular imaging probe tip 20 is constructedin accordance with the principles of the present invention by filling aballoon 30 with Xenon gas 60 as shown in FIGS. 15 and 16. The detectoris then operated as an ionization chamber with the anode formed from awire 64 running through the center of the balloon 30 and the cathode 62formed by embedding wires (or wire mesh) in the balloon as shown in FIG.17. The cathode wires 64, which are at ground potential, can byphysically attached to the inside of the balloon and a furtherinsulating mesh 66 can be attached on the inside of the cathode orsurrounding the anode. An insulated sleeve 68 can be used to give thesystem its positioning information. With the sleeve 68 pulled backcompletely the detector can be operated as a non-imaging highlyefficient counter.

The detector can be operated at 10 and 20 volts on the anode. Protectioncircuitry can be designed to shutdown the supply voltage instantly whenthe current approaches a dangerous level such as one nano-amp. In a gasdetector constructed in accordance with the principles of the presentinvention the conversion of deposited energy is much more efficient thanthe secondary process of scintillation. Thus, although the Xenon gas haslow stopping power relative to a solid or liquid the number of ionspairs still significant. FIG. 18 gives the ion pairs produced as afunction of electron energy at various values of the pressure for a 1 mmdetector. We see that at 10 atm at least 200 ion pairs are produced forall energies. If the balloon is expanded, the number of ion pairs couldincrease to 600. Low noise preamplifiers with 20-100 electrons rms canhandle this number of electrons and provide a good signal to noiseratio. At higher gas pressures there will be a concomitant increase inthe signal as shown in FIG. 18. Pressures up to 10 atm or beyond arepractical.

In another aspect, the present invention provides kits includingcatheters, instructions for use and a package. The catheters willgenerally be those as described above and the instruction for use (IFU)will set forth any of the methods described above. The package may beany conventional medical device packaging, including pouches, trays,boxes, tubes, or the like. The instructions for use will usually beprinted on a separate piece of paper, but may also be printed in wholeor in part on a portion of the packaging. Optionally, the kits caninclude a guidewire, radiopharmaceuticals for bonding to the unstableplaque, or the like.

As will be understood by those of skill in the art, the presentinvention may be embodied in other specific forms without departing fromthe essential characteristics thereof. For example, while someembodiments of the imaging detectors are shown and described as beingdisposed on a balloon, other embodiments of the catheters can bemanufactured without the balloon. Accordingly, the foregoing descriptionis intended to be illustrative, but not limiting, of the scope of theinvention which is set forth in the following claims.

1. An imaging catheter comprising: a catheter body comprising a proximalportion and a distal portion; a flexible membrane disposed at the distalportion of the catheter body, wherein the flexible membrane is movablebetween a deflated position and an inflated position; and an array ofradiation detectors coupled to the flexible membrane.
 2. The catheter ofclaim 1 wherein the radiation detector comprises: a liquid scintillatordisposed within the flexible membrane, wherein the liquid scintillatorcan absorb a beta particle and emit a first scintillation light; and ascintillator optically coupled to a distal end of an optical fiber,wherein the scintillator is disposed within the flexible membrane toabsorb the first scintillation light from the liquid scintillator and totransmit a second scintillation light down the optical fiber.
 3. Thecatheter of claim 2 comprising a moveable shield disposed over thescintillator.
 4. The catheter of claim 2 further comprising aphotodetector coupled to a proximal end of the optical fiber to receivethe second scintillation light.
 5. The catheter of claim 2 wherein thecatheter body comprises a lumen for delivering the liquid scintillatorinto the flexible membrane.
 6. The catheter of claim 2 wherein theflexible membrane in the inflated configuration has a diameter that isbetween approximately two and three times larger than the diameter ofthe flexible membrane in the deflated configuration.
 7. The catheter ofclaim 2 wherein the scintillator has a length between approximately fivecentimeters and ten centimeters.
 8. The catheter of claim 2 wherein thefirst scintillation light has a shorter wavelength than the secondscintillation light transmitted down the optical fiber.
 9. The catheterof claim 1 wherein the radiation detectors comprise a series ofsemiconductor radiation detectors attached to the flexible membrane. 10.The catheter of claim 9 wherein the semiconductor detectors are Si-pindiodes.
 11. The catheter of claim 9 wherein the flexible membrane in theexpanded configuration presses the semiconductor radiation detectorsagainst a radiopharmaceutical coupled to a wall of a body lumen.
 12. Thecatheter of claim 9 wherein the flexible membrane comprises an inner andouter layer, wherein the semiconductor radiation detectors are disposedbetween the inner and outer layer.
 13. The catheter of claim 9 whereinthe flexible membrane in the inflated configuration is filled withXenon.
 14. The catheter of claim 1 further comprising: an innerelectrode disposed within the flexible membrane; a moveable insulatingsleeve disposed over the inner electrode; an outer electrode attached tothe flexible membrane; and an Xenon gas disposed in the flexiblemembrane.
 15. The catheter of claim 14 further comprising a meshinsulator disposed between the outer electrode and the inner electrode.16. A method of locating and characterizing radiopharmaceuticals in abody lumen, the method comprising: advancing a catheter through the bodylumen; and expanding a flexible membrane on the catheter to move theradiation detectors closer to the radiopharmaceuticals in the bodylumen.
 17. The method of claim 16 comprising operating the radiationdetectors in search mode to determine the presence ofradiopharmaceuticals in the body lumen.
 18. The method of claim 17wherein expanding is carried out when it is determined from the searchmode that a concentration of radiopharmaceuticals are present in theportion of the body lumen.
 19. The method of claim 18 comprisingswitching the radiation detectors to an imaging mode to obtain a highresolution of the radiopharmaceuticals.
 20. The method of claim 16comprising attaching the radiopharmaceuticals to unstable plaque. 21.The method of claim 16 wherein the radiation detectors comprise asemiconductor radiation detector, a scintillator, an ionization chamber,or an imaging plate.
 22. The method of claim 16 wherein the flexiblemembrane is in a deflated configuration during advancing.
 23. The methodof claim 16 wherein the radiation detectors provide a spatial resolutionof one millimeter to three millimeters.
 24. The method of claim 16wherein advancing comprises moving the catheter over a guidewire. 25.The method of claim 16 comprising transmitting information from theradiation detector to data acquisition electronics.
 26. A kitcomprising: a catheter comprising at least one radiation detectordisposed on an expandable flexible membrane; instructions for usecomprising advancing the catheter to a target site and expanding theballoon from a deflated configuration to an expanded configuration; anda package adapted to contain the device and the instructions for use.